The blood-brain barrier (BBB), a dynamic and selective interface between the blood and brain parenchyma, consists of endothelial cells ensheathed by glia that line brain microvessels. Preliminary data suggest that perivascular astrocytes and glucocorticoids (i.e. dexamethasone) modulate the induction and maintenance of BBB function, however, mechanisms of action for glia and dexamethasone (DEX) on the BBB are largely unknown. The notion that glial influences are essential for the induction and-maintenance of the i3BB, together with the fact that intraluminal flow causes further differentiation of EC, has prompted the development of sophisticated in vitro models of the BBB, such as the dynamic in vitro BBB model (DIV-BBB) (41,42,43,44). Recent advances in molecular biotechnology have produced tools capable of analyzing patterns of changes in gene expression (i.e. cDNA array hybridization) on a comprehensive scale at distinct time points in a biological process. Applying these tools to the study of BBB induction will provide insight into the critical determinants of endothelial differentiation and BBB repair mechanisms. We hypothesize that 1) endothelial cell changes in gene expression can be identified and characterized at distinct time points which correlate with phenotypic changes; and that 2) DEX may affect non-brain endothelial pathways of gene expression-phenotypic changes similar to those observed during normal BBB induction by glia. A systematic study of this complex biological process has not been performed and would provide valuable insight into strategies for the treatment of human disease and CNS drug delivery.